Microscopic Polyangiitis

Key Features

Essentials of Diagnosis

• Necrotizing vasculitis of small- and medium-sized arteries and veins

• Most common cause of pulmonary-renal syndrome: diffuse alveolar hemorrhage and glomerulonephritis

• Associated with antineutrophil cytoplasmic antibody (ANCA) in 75% of cases

General Considerations

• A pauci-immune nongranulomatous necrotizing vasculitis that

  • Affects small blood vessels (capillaries, venules, or arterioles)

  • Often causes glomerulonephritis and pulmonary capillaritis

  • Often is associated with ANCA on immunofluorescence testing (directed against MPO, a constituent of neutrophil granules)

• Appears in a spectrum overlapping with both polyarteritis nodosa and granulomatosis with polyangiitis (formerly Wegener granulomatosis) because it

  • May involve medium-sized as well as small blood vessels

  • Tends to affect capillaries within the lungs and kidneys

• Rarely, medications induce a systemic vasculitis associated with high titers of p-ANCA and features of microscopic polyangiitis, particularly

  • Propylthiouracil

  • Hydralazine

  • Allopurinol

  • Penicillamine

  • Minocycline

  • Sulfasalazine

Clinical Findings

Symptoms and Signs

• "Palpable" (or "raised") purpura and other signs of cutaneous vasculitis (ulcers, splinter hemorrhages, vesiculobullous lesions)

• Pulmonary-renal syndromes (eg, anti-glomerular basement membrane disease)

• Interstitial lung fibrosis that mimics usual interstitial pneumonitis

• Pulmonary hemorrhage may occur

• Vasculitic neuropathy (mononeuritis multiplex)

Differential Diagnosis

• Polyarteritis nodosa

• Granulomatosis with polyangiitis

Diagnosis

Laboratory Tests

• Microscopic hematuria, proteinuria, and red blood cell casts may be present in the urine

• Elevated acute-phase reactants are typical of active disease

• 75% of patients are ANCA-positive, usually with anti-myeloperoxidase antibodies (MPO-ANCA) that cause a p-ANCA pattern on immunofluorescence testing

• ANCA directed against proteinase-3 (PR3-ANCA) can also be observed

• Pathologic findings in the lung are typically those of capillaritis

• The renal lesion is a segmental, necrotizing glomerulonephritis, often with localized intravascular coagulation and the observation of intraglomerular thrombi upon renal biopsy

Treatment

Medications

• Treated in the same way as granulomatosis with polyangiitis

• Patients with severe disease, typically involving pulmonary hemorrhage and glomerulonephritis, require urgent induction treatment with corticosteroids and either cyclophosphamide or rituximab

• If cyclophosphamide is chosen, it may be administered either in an oral daily regimen or intravenously

• Following successful induction of remission, maintenance treatment should be continued with rituximab (first line) or methotrexate or mycophenolate (second line)

• In cases of drug-induced MPO-ANCA-associated vasculitis,

  • The offending medication should be discontinued

  • Significant organ involvement (eg, pulmonary hemorrhage, glomerulonephritis) requires immunosuppressive therapy

Outcome

Prognosis

• Early diagnosis is key to a good outcome

• Compared with patients who have granulomatosis with polyangiitis, those with microscopic polyangiitis are more likely to have significant fibrosis on renal biopsy because of later diagnosis

When to Refer

• Refer to a ...